EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells

doi:10.18632/oncotarget.7633

科研成果详情

题名	EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells
作者	Zou, Peng1,2; Xia, Yiqun3; Chen, Weiqian2; Chen, Xi 2; Ying, Shilong 2; Feng, Zhiguo 2; Chen, Tongke 2; Ye, Qingqing 2; Wang, Zhe2; Qiu, Chenyu2; Yang, Shulin 1; Liang, Guang2
发表日期	2016-04-05
发表期刊	ONCOTARGET 影响因子和分区
语种	英语
原始文献类型	Article
关键词	thioredoxin reductase 1 reactive oxygen species EF24 ER stress gastric cancer
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; PHASE-III ; ER STRESS ; MITOCHONDRIAL DYSFUNCTION ; 1ST-LINE THERAPY ; OXIDATIVE STRESS ; CARCINOMA CELLS ; CURCUMIN ; CISPLATIN ; ANALOGS
摘要	Gastric cancer (GC) is one of the leading causes of cancer mortality in the world, and finding novel agents for the treatment of advanced gastric cancer is of urgent need. Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, exhibits potent anti-tumor activities by arresting cell cycle and inducing apoptosis. Although EF24 demonstrates potent anticancer efficacy in numerous types of human cancer cells, the cellular targets of EF24 have not been fully defined. We report here that EF24 may interact with the thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, to induce reactive oxygen species (ROS)-mediated apoptosis in human gastric cancer cells. By inhibiting TrxR1 activity and increasing intracellular ROS levels, EF24 induces a lethal endoplasmic reticulum stress in human gastric cancer cells. Importantly, knockdown of TrxR1 sensitizes cells to EF24 treatment. In vivo, EF24 treatment markedly reduces the TrxR1 activity and tumor cell burden, and displays synergistic lethality with 5-FU against gastric cancer cells. Targeting TrxR1 with EF24 thus discloses a previously unrecognized mechanism underlying the biological activity of EF24, and reveals that TrxR1 is a good target for gastric cancer therapy.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503107, 81573657]; Zhejiang Province Natural Science Funding of China [LY16H310011, LY13H160022]; Priority Academic Program Development of Jiangsu Higher Education Institutions, Laboratory animal science and technology plan projects of Zhejiang Province [2014C37006]; Wenzhou science and technology project [Y20140217]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	7 期号:14 页码:18050-18064
DOI	10.18632/oncotarget.7633
页数	15
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000375699000061
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
Pubmed记录号	26919110
PMC记录号	PMC4951270
Scopus记录号	2-s2.0-84975518639
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China
scopus学科分类	Oncology
引用统计	被引频次：40[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/16691
专题	药学院（分析测试中心）附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_内科学_消化内科
通讯作者	Liang, Guang
作者单位	1.School of Environmental and Biological Engineering,Nanjing University of Science and Technology,Nanjing, Jiangsu,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou, Zhejiang,China; 3.Department of Digestive Diseases,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Zou, Peng,Xia, Yiqun,Chen, Weiqian,et al. EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells[J]. ONCOTARGET,2016,7(14):18050-18064.
APA	Zou, Peng., Xia, Yiqun., Chen, Weiqian., Chen, Xi., Ying, Shilong., ... & Liang, Guang. (2016). EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells. ONCOTARGET, 7(14), 18050-18064.
MLA	Zou, Peng,et al."EF24 induces ROS-mediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells".ONCOTARGET 7.14(2016):18050-18064.